Bone, aging metabolism, vitamin

T FIGURE 10-20 Vitamin D3 production and metabolism, (a) Cholecalciferol (vitamin D3) is produced in the skin by UV irradiation of 7-dehydrocholesterol, which breaks the bond shaded pink. In the liver, a hydroxyl group is added at C-25 (pink) in the kidney, a second hydroxylation at C-1 (pink) produces the active hormone, 1,25-dihydroxycholecalciferol. This hormone regulates the metabolism of Ca2+ in kidney, intestine, and bone, (b) Dietary vitamin D prevents rickets, a disease once common in cold climates where heavy clothing blocks the UV component of sunlight necessary for the production of vitamin D3 in skin. On the left is a 21/2-year-old boy with severe rickets on the right, the same boy at age 5, after 14 months of vitamin D therapy. 

Yamaguchi, M., K. Ozaka, and Y. Suketa. 1989a. Alteration in bone metabolism with increasing age effects of zinc and vitamin D3 in aged rats. Jour. Pharmacobio-Dynamics 12 67-73. 

Spontaneous reports of osteoporosis, osteopenia, bone fractures, and delayed healing of bone fractures have been seen in the isotretinoin population. While causality to isotretinoin has not been established, an effect cannot be ruled out. Physicians should use caution when prescribing isotretinoin to patients with a genetic predisposition for age-related osteoporosis, a history of childhood osteoporosis conditions, osteomalacia, or other disorders of bone metabolism. This would include patients diagnosed with anorexia nervosa and those who are on chronic drug therapy that causes drug-induced osteoporosis/osteomalacia and/or affects vitamin D metabolism, such as systemic corticosteroids and any anticonvulsants. 

Immunoreactive parathyroid hormone concentrations may be increased by anticonvulsants, while bone mineral content is reduced. Hypocalcemia and osteopenia can occur, despite normal serum concentrations of active vitamin D metabolites, suggesting that they may be independent of drug effects on vitamin D metabolism. Bone biopsies have shown increased osteoid but normal calcification front formation, accelerated rate of mineralization, and reduced mineralization lag time, suggesting increased skeletal turnover rather than osteomalacia (96). The risk of age-related fractures in drug-treated epileptic patients is not greatly increased (97). 

Eastell R, Yergey AL, Vierira NE, Cedel SL, Kumar R, Riggs BL. Interrelationship among vitamin D metabolism, true calcium absorption, parathyroid function, and age in women evidence of an age-related intestinal resistance to 1,25-dEiydroxyvitamin D action. J Bone Miner Res 1991 6 125-32. 

Hypocalcemia can result from inadequate dietary intake, decreased fractional calcium absorption (as seen with increasing age), or enhanced calcium excretion. To restore calcium homeostasis after hypocalcemia, PTH concentrations rise, and vitamin D metabolism increases to enhance intestinal calcium absorption (see Fig. 88-3), renal calcium reabsorption, and bone resorption. Fracture risk is greatest with low calcium intake and low fractional calcium absorption." ... 

Vitamin D is responsible for maintaining calcium homeostasis. Low calcium concentrations lead to hyperparathyroidism and bone resorption. Vitamin D insufficiency (11 to 20 ng/mL) and deficiency (<10 ng/mL) [25(OH) vitamin D measurement, 10 ng/mL = 25 mcmol/L] is becoming more commonly recognized in all age groups, ° especially malnourished individuals, northerners, women wearing veiled dresses, African-Americans, seniors, and long-term care residents. Low vitamin D concentrations resnlt from insufficient intake, decreased sun exposure, decreased skin production, decreased liver and renal metabolism, and winter residence in northern climates. 

Calcium Adequate calcium intake is required to maintain bone mineral density and reduce the risk of osteoporosis in the elderly. In addition to the reduced absorption of calcium by elderly people that results from age-related changes in vitamin D metabolism, the elderly also show a reduced ability to increase the efficiency of calcium absorption as an adaptive response to low-calcium diets. Also, as noted earlier, the low-acid conditions resulting from atrophic gastritis can reduce calcium absorption. Dietary calcium reacts with hydrochloric acid in the stomach to form soluble calcium chloride, which is absorbed in the small intestine. In the United States, the recommended calcium intake is 1200mg/day for men and women older than age 70. Many elderly people may benefit from calcium supplements. 

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